The bones and ligaments of the carpus, or wrist, form a structure that resembles a tunnel. The median nerve enters the hand by passing through the “carpal tunnel” formed by the carpal bones and transverse carpal ligament in the wrist. Carpal Tunnel Syndrome (CTS) is a commonly occurring condition affecting the hand that arises from pressure on the median nerve in the wrist.
CTS is sometimes referred to as median compression neuropathy within the carpal canal. When the median nerve is pinched it causes painful throbbing, tingling and numbness in the hand, wrist and forearm. Furthermore, patients suffering from CTS occasionally have symptoms including swollen hands and wrists. CTS can affect all or any combination of a person's fingers and often results in such extreme weakness, which may result in the inability of the patient to grasp objects as they could before the development of CTS.
CTS is often classified as a Repetitive Motion Injury (“RMI”), since it usually results from continuously repeating the same motion with the hand and wrist. Types of activities that can cause CTS symptoms include extended periods of writing, typing, holding a steering wheel, using power tools, craft work, and sports such as cycling, weightlifting and rowing. Other conditions can also affect CTS, including arthritis, diabetes, alcoholism, thyroid disease, wrist injuries, pregnancy and menopause. CTS affects an estimated 200,000 people a year. In fact, as many as 10% of all adults may experience CTS symptoms at one time or another.
Several treatments have been proposed and are currently used to relieve the symptoms of CTS (Wilson, J. K. et al. (2003), Disabil. Rehabil. 25(3): 113-119). These include surgery, steroid injections into the carpal tunnel, anti-inflammatory drugs, diuretics, and splints. In general, it is often desirable to use a more conservative approach. However, the overall treatment strategy depends on the cause and severity of nerve compression. In the most serious of conditions, surgery is often required to sever the transverse carpal ligament. In less severe cases, and if symptoms are provoked by certain activities, modification of hand use during these activities is generally prescribed. In fact, it is often desirable to eliminate the activity, decrease its duration, or interrupt it with periods of rest. A variety of medications are also used to treat CTS, including corticosteroids and non-steroidal anti-inflammatory (NSAIDs) compounds. These compounds may be used in conjunction with a brace in order to immobilize the wrist, with or without splints, or in conjunction with rehabilitation modalities eg. therapeutic ultrasound, stretching and strengthening, as either a preventive measure or as therapy for CTS.
Seven generally immunologically distinct botulinum neurotoxins have been characterized, these being respectively botulinum neurotoxin serotypes A, B, C1, D, E, F and G, each of which is distinguished by neutralization with type-specific antibodies. The different serotypes of botulinum toxin vary in the animal species that they affect and in the severity and duration of the paralysis they evoke. For example, it has been determined that botulinum toxin type A is 500 times more potent, as measured by the rate of paralysis produced in the rat, than is botulinum toxin type B. Additionally, botulinum toxin type B has been determined to be non-toxic in primates at a dose of 480 U/kg which is about 12 times the primate LD50 for botulinum toxin type A. Botulinum toxin apparently binds with high affinity to cholinergic motor neurons, is translocated into the neuron and blocks the release of acetylcholine. These neurotoxins are known to inhibit acetylcholine release at the neuromuscular junction via at least three different mechanisms. There are currently two botulinum neurotoxins commercially available: Botox™, a type A toxin, and Myobloc™, a type B toxin. Botulinum toxin type A is the most lethal natural biological agent known to man. About 50 picograms of a commercially available botulinum toxin type A (available from Allergan, Inc., Irvine, Calif. under the tradename BOTOX™ (purified neurotoxin complex) in 100 unit vials) is a LD50 in mice (i.e. 1 unit). Thus, one unit of BOTOX™ contains about 50 picograms (about 56 attomoles) of botulinum toxin type A complex. Interestingly, on a molar basis, botulinum toxin type A is about 1.8 billion times more lethal than diphtheria, about 600 million times more lethal than sodium cyanide, about 30 million times more lethal than cobra toxin and about 12 million times more lethal than cholera. Singh, Critical Aspects of Bacterial Protein Toxins, pages 63-84 (chapter 4) of Natural Toxins II, edited by B. R. Singh et al., Plenum Press, New York (1996) (where the stated LD50 of botulinum toxin type A of 0.3 ng equals 1 U is corrected for the fact that about 0.05 ng of BOTOX™ equals 1 unit). One unit (U) of botulinum toxin is defined as the LD50 upon intraperitoneal injection into female Swiss Webster mice weighing 18 to 20 grams each. Myobloc™, a type B toxin, is manufactured by Elan Corporation and is a medication used to treat muscular spasms, for example, it is currently used to successfully treat cervical dystonia, a painful condition characterized by involuntary contractions of the neck and/or shoulder muscles that result in abnormal head positions.
There is a need for a non-surgical treatment alternative for carpal tunnel syndrome that reduces or ameliorates the development of carpal tunnel syndrome, and prevents or ameliorates the pain and paresthesias associated with the condition.